Lectin-like oxidized low-density lipoprotein 1 receptor in a reduced uteroplacental perfusion pressure rat model of preeclampsia.

Preeclampsia is a major cause of maternal and fetal morbidity and mortality that has been associated with endothelial dysfunction attributed, in part, to dyslipidemia, an imbalance in angiogenic factors and oxidative stress. One of the many factors that have been shown to be elevated in women with preeclampsia is low-density lipoprotein (LDL) and the more oxidizable, small dense LDL, which can lead to increased vascular oxidative stress and decreased bioavailability of NO. Lectin-like oxidized LDL-1 receptor (LOX-1) is a specific receptor for oxidized LDL. We hypothesized that a reduction of placental perfusion using a rat model of reduced uteroplacental perfusion pressure would result in enhanced LOX-1 expression in the maternal vasculature causing impaired vascular endothelial function through the actions of increased superoxide production and decreased NO-mediated vasodilation. We demonstrated a significant increase in the expression of the LOX-1 receptor (4.3-fold; P=0.002), endothelial NO synthase (2.7-fold; P=0.001), and superoxide (P=0.02) in thoracic aorta of the reduced uteroplacental perfusion pressure model, whereas maximal vasodilator function was modestly decreased (P<0.05). Endothelial-dependent vasodilator function was unaffected by either oxidized LDL or an LOX-1 receptor inhibitor in controls but was modestly increased in the presence of both oxidized LDL and the LOX-1 receptor inhibitor in reduced uteroplacental perfusion pressure (P=0.03). In summary, we have shown that, in a rat model of preeclampsia, there is a dramatic increase in the expression levels of both the LOX-1 receptor and the endothelial NO synthase enzyme, along with evidence of increased superoxide production and subsequent modestly decreased endothelial function.